The Mechanisms of Cell Signaling Research Core is focused on the mechanisms of signaling by which cells recognize and respond to environmental stresses that influence cell proliferation and survival. Clearly many environmental agents alter key signaling pathways, thus provoking aberrations in the molecular signaling mechanisms that stimulate or suppress cell proliferation or apoptosis. These alterations include activation of oncoproteins, inactivation of tumor suppressors, and modification of apoptotic signaling pathways. Together with genetics, signal transduction has contributed significantly to the current molecular and mechanistic understanding of disorders of cell proliferation and apoptosis, such as cancer and neurodegenerative diseases, that are frequently linked to environmental exposures. Due to the recent explosion in genomic- and proteomic-based research, the Center in Molecular Toxicology has developed a new research core, Mechanisms of Cell Signaling, comprised of investigators with a breadth of research experience and interests that focus on dissecting cellular signaling pathways relevant to toxicology. Members of this Core provide the Center with faculty committed to determining key signaling pathways and analyzing proteins in those pathways that play pivotal roles in cellular outcome. The Core provides considerable expertise upon which other Cores in the Center can develop new understandings and approaches for the analysis of particular signaling pathways. Core membership represents diverse interests within the area of cell signaling. The members include faculty with interests in chemistry and biochemistry, as well as cellular and molecular biology. However, the Core maintains a primary overall focus, analysis of biochemical mechanisms that impact signaling pathways that dictate cell proliferation, DNA repair, and cell survival. The Core has two broad goals: 1) to increase the awareness of research objectives within each laboratory, thereby encouraging collaborative possibilities within the Core and Center, and 2) to provide strong biological expertise for addressing the biological relevance and regulation of other biochemical processes that are the focus of other Research Cores within the Center.